Lamivudine-Induced Liver Injury

Area of Science:

• Pharmacology
• Toxicology
• Hepatology

Background:

• Lamivudine is an antiretroviral drug with low toxicity at prescribed doses.
• Limited research exists on the toxicity and mechanisms of high-dose, prolonged lamivudine administration.
• Investigating liver effects of higher lamivudine doses is crucial.

Purpose of the Study:

• To investigate biochemical and histopathological liver changes in rats after prolonged exposure to high-dose lamivudine.
• To elucidate the mechanism of lamivudine-induced liver toxicity.

Main Methods:

• Administration of lamivudine (4-2500 mg/kg) to chicken embryos and Wistar rats (oral doses up to 500 mg/kg for 15 or 45 days).
• Biochemical assays for serum enzymes (ALT, AST, GGT), total protein, and liver enzymes (GST, GGT, SOD), MDA, and protein.
• Histopathological examination of liver tissues.

Main Results:

• LD50 determined as 427 mg/kg in vitro.
• Significant reduction in total serum protein and increased enzyme activities observed at 500 mg/kg in repeat-dosed rats.
• Elevated hepatic GGT, GST, SOD, and MDA at 20 mg/kg, with hydropic hepatocyte degeneration at doses ≥ 100 mg/kg.

Conclusions:

• Lamivudine toxicity in rat liver is associated with oxidative stress.
• High-dose lamivudine induces significant biochemical and histopathological changes in the liver.
• Further research into lamivudine's long-term effects is warranted.